Overexpression of Protein Kinase C β Isoform by Adenoviral Gene Transfer Accelerated Intimal Hyperplasia in Rat Carotid Artery
Year: 2001
Type: article
Abstract: : Vigorous restenosis is responsible for high failure rates of angioplasty in diabetic patients. Since protein kinase C (PKC)β isoform activation is associated with vascular complications of diabetes, we have determined whether PKCβ isoform overexpression can stimulate growth and migration of vascular smooth muscle cells (SMCs) and cause an acceleration of arterial intimal hyperplasia. Overexpression of PKCβ1 (adv-PKCβ1) or β-galactosidase (adv-βgal) were achieved using replication-deficient adenovirus vectors in cultured rat aortic SMCs and rat carotid arteries after balloon injury. Rat aortic SMCs infected with adv-PKCβ1 at 10９ PFU／ml increased PKC activity and PKCβ1 isoform protein level by more than 10-fold com-pared to adv-βgal infected SMCs at 4 days after infection. The growth and migration rates in PKCβ1 over-expressed SMCs were increased by 1.5- to 1.9-fold compared to adv-βgal infected SMCs. Protein levels of PKCβ1 isoform in adv-PKCβ1 infected arteries were increased by 4.2- and 2.0-fold compared to non-infected and adv-βgal infected arteries, respectively, at 7 days after adenovirus infection. Ratio of intima／media area, a marker of restenosis, were 0.26±0.08 and 0.54±0.14 (p<0.05) at 7 days after infection in adv-βgal and adv-PKCβ1 infected arteries, respectively. Thus, overexpression of PKCβ isoform can enhance vascular SMCs migration and growth, causing an accelerated rate of intimal hyperplasia, and may involve the restenotic process after angioplasty in diabetic patients. Key words: protein kinase C, restenosis, gene transfer, diabetes.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W273558165